The purpose of this Mentored Patient-Oriented Research Career Development Award (K23) is to enable the candidate to become an independent researcher investigating genetic contributions to developmental psychopathology under conditions of adversity. The research goal is to study the pleiomorphic psychopathologic expression of promising genetic markers under varying conditions of adversity across childhood and adolescence. To prepare for this research, the training program focuses on integrating skills in developmental epidemiology with molecular genetics, statistical genetics, and ethical, legal, and social issues. This training will include working directly with Drs. Costello and Sullivan on two GWAS projects. The candidate is based in the Center for Developmental Epidemiology, Duke University Medical Center. Sponsors include Jane Costello PhD (developmental psychopathology and comorbidity), Patrick Sullivan MD FRANZCP (psychiatric geneticist), David Goldstein, PhD (population and molecular geneticist), Elizabeth Mauser, PhD (statistical geneticist), and Robert Cook-Deegan, MD (ethical, legal, and social issues of genetics and genomics). The research plan proposes to study gene-environment interaction models for (1) promising genetic markers include HTTLPR, HTR2A T102C, MAOA-u VNTR, BDNF va!66met and COMT val158met and additional markers identified based upon the results of psychiatric GWAS studies, (2) four environment risk categories (i.e., negative life events, potentially traumatic events, chronic stressors, and empirically-derived adversity profiles), (3) two outcomes (i.e., anxiety and depressive symptoms), and (4) two developmental periods (i.e., childhood and adolescence). Hypotheses will be tested in a population-based sample of children (CCC study;1627 assessments of 920 subjects aged 9-17) and then retested in another longitudinal sample (GSMS study;8804 assessments of 1420 subjects aged 9-21, up to 10 assessments per subject). The application will also support preparation and submission by the investigator of an R01 application following up with vulnerable subgroups identified in the current analysis to study neurobiological mediators of genetic risk. This work provides a framework for unpacking the complex expression of genetic risk in response to environmental and developmental variations. Identifying high-risk groups can inform prevention and treatment interventions and our understanding of the etiology of childhood psychopathology.